March 2015: Post summaries and take home points

Eosinophils are white blood cells that have granules like mast cells.
Mast cells and eosinophils are often found together in late and chronic stages of allergic inflammation.
Mast cells, eosinophils and their effects on the body are collectively called “the allergic effector unit”.
Mast cells release signals that affect eosinophil behavior and receive signals from eosinophils. The reverse is also true.
Mast cells and eosinophils can activate each other and cause mediator release.
Eosinophils make mast cells more responsive to IgE.
When mast cells and eosinophils are in contact, eosinophils live longer than usual.

S1P is involved in development of vessels, vascular permeability and immune function.
Receptors for S1P are found on many cell types, including mast cells.
When the IgE receptor on mast cells is stimulated, S1P is produced and secreted.
Histamine can stimulate S1P production.
S1P regulates blood pressure and heart rate.
S1P is involved in anaphylaxis recovery and probably helps to counteract low blood pressure.

Toll like receptors (TLRs) are receptors that bind products from bacteria, fungi and viruses to fight infection.
TLRs are found on mast cells.
When TLRs are bound, mast cells secrete inflammatory molecules like TNF, IL-6, IL-13 and IL-1b.
TLRs function independently of IgE.

Leptin is a hormone mostly released by adipose tissue, but also by mast cells.
Leptin is a “starvation” signal sent to the brain.
Patients with obesity have higher circulatory leptin than those without obesity.
Patients with obesity are more resistant to the effects of leptin, so they often feel hungry even if they have eaten.
Leptin actives inflammatory cells and induces production of TNF, IL-2 and IL-6.
Leptin suppresses signals from the IgE receptor to make mediators.
High levels of leptin may suppress ghrelin, the “hunger” hormone.

TLRs are found on several cell types, including mast cells.
Unlike many receptors that only have one “matching” molecule, TLRs bind lots of molecules.
These molecules are usually from infecting organisms.
Some molecules induce production of cytokines.
Some molecules, like peptidoglycan from bacterial cell walls, may induce degranulation.
Viral, fungal and bacterial infections can all cause mast cell activation.

High levels of glucocorticoids deplete mast cell populations.
Glucocorticoids interfere with production and release of stem cell factor, a mast cell growth factor.
Glucocorticoids decrease mast cell growth and activity.
The mechanism by which this occurs is thought to involve insulin.
Insulin activates mast cell signaling pathways.
Activity in the HPA axis, which regulates steroid levels, is increased in type I and II diabetes, causing elevated cortisol.
Hypoglycemia can cause mast cell degranulation.
Anaphylaxis can cause hypoglycemia.

Type I and II diabetes can protect against anaphylaxis and allergic reactions.
Mast cells are involved in development of glucose intolerance and insulin resistance.
In mice with type II diabetes, mast cell stabilizers protects against glucose intolerance and insulin resistance.
In a patient with type II diabetes, treatment with cromolyn normalized plasma glucose and A1C.
Type I diabetes has a more complicated relationship with mast cells.
Diabetes reduces mast cell degranulation.

Osteosclerosis is hardening of the bones.
Osteoblast is the cell type that makes new bone.
In osteosclerosis, osteoblasts may lay down new bone faster than osteoclasts can eat up old bone.
Osteolysis occurs when abnormal cells grow rapidly and inhibit osteoblasts, and osteoclasts do not work fast enough.
It is not clear if having osteosclerosis makes progression of SM more likely.
People with all forms of SM have been found ot have osteosclerosis.
Osteosclerosis with swelling of liver and spleen, presence of CKIT mutation in multiple cell types and high increase of baseline serum tryptase warrants careful monitoring.
For mast cell disease, large osteolytic lesions are the “worst” bone involvement because it immediately classifies you as ASM.
Multiple bone breaks due to severe osteoporosis also classifies you as ASM.

Osteoporosis is the most common form of bone involvement in SM.
Osteoporosis is more common in mast cell patients than in the general population.
Patients with rapidly increasing serum tryptase and those without have similar incidence of osteoporosis.
Patients with rapidly increasing serum tryptase were more likely to develop osteosclerosis during the period of the study.

Overall, about half of SM patients have bone involvement.
Markers associated with both bone resorption and bone formation were higher in mastocytosis patients.
Osteoprotegerin is higher in mastocytosis patients. This protein regulates the activity of osteoclasts.
Levels of c-telopeptide were significantly higher in patients with SM-AHNMD and ASM than in ISM or CM.
Presence of skin lesions does not change risk for osteoporosis.
Bone mineral density and serum tryptase do not correlate with serum markers of bone turnover.

In osteosclerosis, your body makes new bone faster than it resorbs it.
In osteoporosis, your body resorbs bone faster than new bone is made.
In osteolysis, your body resorbs bone faster than new bone is made, but much worse than in osteoporosis.
Both osteoporosis and osteolysis can cause pathological fractures.
Osteoporosis does not classify you as having ASM.
Osteoporosis that caused multiple fractures classifies you as having ASM.